Virus crystallisation

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Comparison between crystallisation of salt (left) and Tobacco Mosaic virus (right) as seen through electron microscopy. Biology and man (1944) (19762396143).jpg
Comparison between crystallisation of salt (left) and Tobacco Mosaic virus (right) as seen through electron microscopy.

Virus crystallisation is the re-arrangement of viral components into solid crystal particles. [1] The crystals are composed of thousands of inactive forms of a particular virus arranged in the shape of a prism. [2] The inactive nature of virus crystals provide advantages for immunologists to effectively analyze the structure and function behind viruses. Understanding of such characteristics have been enhanced thanks to the enhancement and diversity in crystallisation technologies. Virus crystals have a deep history of being widely applied in epidemiology and virology, and still to this day remains a catalyst for studying viral patterns to mitigate potential disease outbreaks.

Contents

Historical background

Pre-20th century

Virus crystals originate back to the late 19th century where the first protein crystallisation discoveries were made by German biologists Ritthausen and Osborne, mainly for hemoglobin in worms and fishes. [3] These early observations were primarily regarded as laboratory curiosities. What began as mere curiosities evolved into the need for purification and isolation of proteins for clearer visualisation, thus leading to protein crystallisation. Protein crystallisation techniques were ultimately introduced in virology after the rise of the Tobacco Mosaic Viruses (TMV), which were the first ever viruses to be discovered. [4]

1930s

Achieving clear visualisation of viruses using limited technology, such as microscopy was difficult due to their relatively miniature size, with the smallest of viruses measuring in at roughly 20 nm in diameter. [5] Microscopy was therefore a relatively challenging field, with alternative methods of observation in high demand. TMV viruses were first crystallised by Wendell Stanley, who demonstrated that TMV viruses retained its infectivity even in crystal form. [3] It was during this time when researchers discovered that crystallised viruses (much like proteins and other organic molecules) could diffract X-rays, implying a complex structural mechanism in viral bodies. This breakthrough served as the basis for the expansion of virology into X-ray crystallography. [3]

1950s, 1960s

Crystals of the Satellite Tobacco Mosaic Virus (STMV) with different geometries allow for different perspectives of visualisation. Both orthorhombic crystals (left) and cubic crystals (right) come in equivalent sizes. Satellite tobacco mosaic virus crystal.jpg
Crystals of the Satellite Tobacco Mosaic Virus (STMV) with different geometries allow for different perspectives of visualisation. Both orthorhombic crystals (left) and cubic crystals (right) come in equivalent sizes.

X-ray crystallography was developed during the mid 20th century by scientists' efforts to study the characteristics of crystallised viruses in laboratory investigations. Amongst them was Dorothy Hodgkin, an expert in molecular microbiology, who determined TMV structure through virus crystals that could diffract X-ray. [7] This discovery served as a basis to continuous refinement in methods of virus crystallography, which later led to the determination of numerous other virus structures, including the poliovirus, rhinovirus, and Human retrovirus (HIV). Such advancements provided valuable insights into the mechanisms of viral infection and replication, thus facilitating the development of antiviral drugs and vaccines heading into the late 20th century.

1990s-Today

It was towards the end of the 20th century when scientists realized viruses surrounded with thick lipid membranes were unable to form ordered crystals. [3] Such viruses made it difficult to properly obtain X-ray diffraction results. [3] In response to this, cryogenic electron microscopy (cryo-EM) emerged as a new, alternative method for studying virus structures. Cryo-EM enables scientists to visualise viruses at near-atomic resolution without crystallisation. [3] Combination of both X-ray crystallography and cryo-EM have contributed towards the field of virus morphology and behaviour in the immune system. Such advancements in technology have not only shed light on viral characteristics, but has revolutionized virology as a whole, and continue to be subject to heavy focus to this day.

Viral structure and behaviour

Viruses are defined as “obligate intracellular parasites” that contain DNA or RNA in the viral genome core, and are encased by a protective protein coat. [8] Generally, the core is encased in capsid proteins in a single or double-layered structure. [8] Some viruses, such as some Coronaviruses, also develop a large lipid membrane known as the envelope when found in particular hosts. [9] This membrane is composed of a lipid bilayer surrounding a layer of membrane-bound proteins, with either surface glycoproteins or spike proteins protruding from the extracellular aspect. Such viral envelope is usually acquired when travelling through the plasma or intracellular matrices of the host organism and may vary in composition depending on the host cell's membrane lipid content and host cell proteins. [8] The structure of note for crystallisation and identification is the capsid protein structure. Viruses are majorly icosahedral in structure, with the second most common organisation being a helical, spring-like, structure. [10] Viral capsid structures are organised in such a way as to maximise the efficiency of carrying its specific length of RNA or DNA chain. [11] The kinetics of the capsid proteins may also play a role in its organisation, though this has not yet been fully elucidated. [12] The symmetry and geometry of viruses is facilitated by the crystallisation of viruses (and more specifically their capsid protein subunits) in order to study protein-protein interactions; a proxy for the capsids' properties and functions. [1]

Helical capsid structure

Schematic model showing the helical capsid structure of the Tobacco Mosaic virus (TMV). Tobacco mosaic virus structure.png
Schematic model showing the helical capsid structure of the Tobacco Mosaic virus (TMV).

The helical capsid structure is majorly dependent on the length of the viral RNA or DNA genome. [11] Due to the nature of packing identical asymmetric proteins with no rotational symmetry in order to minimise disturbance to protein-protein bonds at specific binding and receptor sites, capsid protein structures composed of a repetition of identical protein subunits necessarily arranges itself into a lattice that folds to encase its contents in a helical structure, much like the naturally occurring helical structure seen in DNA. [11] This resultant helical structure is the case due to the geometric limitations and symmetrical nature necessitated by the protein sub-assembly array and its protein-protein interactions. [11] The Tobacco Mosaic Virus studied by Caspar and Klug in their 1962 crystallisation study was discovered to be composed of a '2 to 5 capsid protein subunit aggregate', arranged in a helical capsid structure. [11]

Icosahedral capsid structure

(Left) Ribbon diagram showing the asymmetrical capsid structural aggregate of the Foot-and-mouth disease virus (FMDV), a repeating subunit that makes up its spherical capsid structure. (Right) Image of the 3D icosahedral symmetry of the capsid. Protein chains VP1, VP2, VP3, and VP4 individually derive from smaller structural protein components of the capsid. FMDV icosahedral capsid.jpg
(Left) Ribbon diagram showing the asymmetrical capsid structural aggregate of the Foot-and-mouth disease virus (FMDV), a repeating subunit that makes up its spherical capsid structure. (Right) Image of the 3D icosahedral symmetry of the capsid. Protein chains VP1, VP2, VP3, and VP4 individually derive from smaller structural protein components of the capsid.

The Icosahedral capsid structure is majorly dependent on the energy efficiency and geometric limitations of the packaging of the genome. [11] Similar to the constraints that lend to the symmetrical nature of the helical capsid structure, specific geometric limitations naturally and necessarily apply on the possible conformations of the encasing structure. The icosahedral capsid structure is the most common arrangement due to 2-3-5 symmetry of its namesake shape, allowing for the use of up to the greatest number (60 units) of triangular “identical symmetrical units” to construct a 'spherical' shell to enclose some given material at any given size. [12] In terms of optimising the ratio of number of required protein sub-assemblies and the surface area enclosed, icosahedral symmetry is again found to be the smallest and most efficient symmetry to adopt. [11] Icosahedral capsid structure is an optimal design for encasing material due to its geometric and symmetric properties, lending to its efficient design being naturally and necessarily adopted by a majority of viral lineages. [11] The symmetrical and highly-order nature of most virus crystals can be attributed to the inherent symmetry of the icosahedral capsid structure and its protein-protein interactions. [1]

Viral behaviour

Viruses generally invade and hijack host cells as a method of replication. [13] Once infected, the host cell has its cellular processes compromised as virally encoded proteins are produced from virus replication and propagation. [13] This process consists of Protein-protein interactions of the primary and tertiary structure of the capsid, and is subject to heavy focus for better understanding of the molecular and biochemical mechanisms of viral behaviour. [1]

Crystallisation procedure

The aim of crystallisation is to grow suitable sized, high quality virus crystals in order to be read properly during the imaging process. [1] Artificial crystallisation in the laboratory is generally carried out in four major steps:

NASA engineer Michael Hopkins loading protein crystallography plates with prepared protein solutions for the Phase II Real-time Protein Crystal Growth experiment ISS-64 Hopkins loads protein crystallography plates 1.jpg
NASA engineer Michael Hopkins loading protein crystallography plates with prepared protein solutions for the Phase II Real-time Protein Crystal Growth experiment

1. Propagation

Viruses of specific species are placed in incubators with healthy cells, which mimics their ideal conditions for proper functioning. [3] With the presence of healthy cells, viruses attach and undergo replication to produce large samples. [13]

2. Extraction and purification (isolation)

The replicated virus particles are extracted, which is followed by purification to remove unwanted substances such as debris. [3] This process isolates virus particles and leaves them in high concentration solutions. [3] They then undergo centrifugalizing, which separates the liquid supernatant from the solid virus precipitate. [3] This process is repeated until the precipitate is further densified into a virus pellet. [3]

3. Nucleation

Concentrated virus pellets are treated with reagents that allow them to form small crystal nuclei. Such stages are referred to as nucleation, a critical process during the early stages of crystallisations, where small clusters of coat proteins aggregate to form the building blocks of the outer capsid structure. [15] Some coat proteins are charged and produce electrostatic repulsion, which needs to be overcome by hydrophobic interactions in order to crystallise the capsid. [15] Hydrophobic interactions refer to the tendency of nonpolar regions of molecules that associate with each other strongly in aqueous environments, but minimize contact with water. [16]

4. Crystal growth

Virus crystals are typically grown in vitro once initial crystal nuclei are formed. [17] The growth of virus crystals can be influenced by various factors such as temperature, pH, and the presence of specific additives or precipitants in the solution. [3] When successful, viral particles align and associate with each other in a regular pattern forming repeating three dimensional lattices. [3] The growth process can take hours to days, depending on the virus and the crystallisation conditions.

Imaging techniques

Crystalline structures of virus crystals undergo imaging to produce visual results. They are developed to obtain information on microscopic arrangements in immobilized virus particles. Imaging has improved over time as advancements in X-ray sources, detectors and computer based imaging programs enhanced feasibility in procedures such as X-ray crystallography and cryogenic electron microscopy. [18]

X-ray crystallography

Shown here is the X-ray crystallography determined structure of a virion of Enterobacteria phage PRD1, a type of tectivirus from the genus Alphatectivirus in 2-fold symmetry view. Virus crystals amplify weak signals from the scattering of diffracted X-rays by individual atoms and virus particles. Precise atomic positions and arrangement of capsid proteins are generated under high resolution. F30-01l-9780123846846.png
Shown here is the X-ray crystallography determined structure of a virion of Enterobacteria phage PRD1, a type of tectivirus from the genus Alphatectivirus in 2-fold symmetry view. Virus crystals amplify weak signals from the scattering of diffracted X-rays by individual atoms and virus particles. Precise atomic positions and arrangement of capsid proteins are generated under high resolution.

X-ray crystallography utilizes virus crystals’ ability to diffract electromagnetic waves upon exposure. [21] Diffraction in this case refers to the interference of scattered waves emitted in different directions across the lattice. [21] Diffraction patterns depend on internal order within the crystal. [3] High internal order with dense arrangements produce more extensive diffraction patterns with higher resolution, allowing for more precise determination of atomic positions. [3] An X-ray diffractometer is used to measure the crystal's ability to diffract waves upon being exposed to the X-ray source. [21]

X-ray crystallography does not guarantee accurate performance for all virus crystals. For example, virus crystals at macromolecular size have significant limitations compared to smaller crystals. [3] They are softer and are more susceptible to damage, and can easily disintegrate over high radiation. [3] This results from the significant amount of liquid between molecules, with approximately 50% solvent content on average. [3] The solvent consists of water and other small molecules that freely diffuse through the crystal's interstitial spaces. [3] Such unwanted presence of solvent-filled channels within macromolecular crystals hinder the reading of X-ray diffraction patterns. [3]

Cryogenic electron microscopy (Cryo-EM)

Cryogenic electron microscopy (Cryo-EM) utilizes the kinetics of a beam of electrons to detect and image a sample. [22] Cryo-EM provides an overall improved performance over the traditional light microscope due to its higher resolution and magnification. [22]

In cryo-EM, crystallisation is not necessary and can directly observe biological samples, such as infected host cells and active viruses. [17] This provides significant advantages over X-ray crystallography when investigating complex viral structures that pose challenges during crystallisation. It is particularly useful in observing the conformational changes of the virus, which is difficult to achieve via crystallisation. [17]

However, despite Cryo-EM being able to provide higher resolution over light microscopes, it is not enough to exceed that of X-ray crystallography. [17] X-ray crystallography still remain as the most suitable approach when taking into account atomic level structures and micro-molecular interactions. [17] Researchers therefore combine both cryo-EM and X-ray crystallisation as a method of overcoming each other's limitations.

Advances in imaging technology

Five major stages are involved in a typical cryo-EM experiment: sample preparation, grid preparation, data collection, image processing, and structure determination. The reconstruction of a 3D density map is derived upon its 2D model, which allows for clearer visualisation of the structure for the sake of better understanding of its morphology. Cryogenic electron microscopy workflow.svg
Five major stages are involved in a typical cryo-EM experiment: sample preparation, grid preparation, data collection, image processing, and structure determination. The reconstruction of a 3D density map is derived upon its 2D model, which allows for clearer visualisation of the structure for the sake of better understanding of its morphology.

Recent advancements in cryo-electron microscopy (cryo-EM) have expanded the extent in which virus morphology could be uncovered by researchers. Cryo-EM began to feature direct electron detectors (DEDs), which involve direct conversion of ejected electrons into electrical signals, thus improving the speed and feasibility of the imaging procedure. [23] Limitations with studying large molecular complexes were combated with the introduction of cryo-electron tomography (cryo-ET) . This is an alternative to cryo-EM that allows for visualisation of the environment and interaction outside of the virus inhabited host cell. [23] Such advancements have propelled the understanding of virus activity in its host cell environment, rather than solely focusing on the virus itself. [23]

Advancements in X-ray crystallography under the name of macromolecular crystallography (MX) have also been involved in the image technology overhaul phase. [18] MX is considered a new scientific discipline that adapts advanced tools and automated procedures. This is carried out with synchrotron sources, fast detectors, and innovative sample delivery methods to study the dynamic features of macromolecules. [18] Such technique that observes virus dynamics rather than its static composition is referred to as time resolved crystallography. [18]

Time resolved crystallography is facilitated through X-ray Free Electron Lasers (XFELs), which is a new generation of light sources succeeding the traditional notion of synchrotron radiation, as it allows for more control over light power and range. [18] [24] Despite the rapid evolution cryo-EM that does not require crystallisation, MX and XFELs allow virus crystallisation to remain relevant and continue to play a vital role in providing atomic-level details of viruses. [18]

Undiscovered areas

Whether or not viruses are ‘alive’ is a subject of heavy debate across the world. While viruses exhibit some behaviours that can be characterized as 'alive', such as their ability to replicate and evolve, they lack certain essential features typically associated with life, such as cellular structure and independent metabolism. [25] Overcoming limitations to virus crystallisation can provide important details about unknown molecular interactions that determine their life-like behaviour, thus allowing its characteristics to be comparable with those that belong to a biological kingdom.

Future prospects

With major enhancements being made in X-ray crystallography and cryo-electron microscopy, researchers are shifting their focus back to the growing process of crystals, as they remain as prominent issues by placing limitations on crystal size variability. More emphasis is required on overcoming the limitations to macromolecular crystals, as its demand has been growing amongst researchers. [26] Many viral crystals fall into this category, hence, the traditional crystallisation technique is said to receive more attention heading into the future. [26]

Related Research Articles

<span class="mw-page-title-main">Capsid</span> Protein shell of a virus

A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The proteins making up the capsid are called capsid proteins or viral coat proteins (VCP). The capsid and inner genome is called the nucleocapsid.

<span class="mw-page-title-main">Crystallography</span> Scientific study of crystal structures

Crystallography is the branch of science devoted to the study of molecular and crystalline structure and properties. The word crystallography is derived from the Ancient Greek word κρύσταλλος, and γράφειν. In July 2012, the United Nations recognised the importance of the science of crystallography by proclaiming 2014 the International Year of Crystallography.

<span class="mw-page-title-main">Structural biology</span> Study of molecular structures in biology

Structural biology, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization.

<span class="mw-page-title-main">Picornavirus</span> Family of viruses

Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm icosahedral capsid. The viruses in this family can cause a range of diseases including the common cold, poliomyelitis, meningitis, hepatitis, and paralysis.

Electron crystallography is a subset of methods in electron diffraction focusing just upon detailed determination of the positions of atoms in solids using a transmission electron microscope (TEM). It can involve the use of high-resolution transmission electron microscopy images, electron diffraction patterns including convergent-beam electron diffraction or combinations of these. It has been successful in determining some bulk structures, and also surface structures. Two related methods are low-energy electron diffraction which has solved the structure of many surfaces, and reflection high-energy electron diffraction which is used to monitor surfaces often during growth.

<span class="mw-page-title-main">Transmission electron cryomicroscopy</span>

Transmission electron cryomicroscopy (CryoTEM), commonly known as cryo-EM, is a form of cryogenic electron microscopy, more specifically a type of transmission electron microscopy (TEM) where the sample is studied at cryogenic temperatures. Cryo-EM, specifically 3-dimensional electron microscopy (3DEM), is gaining popularity in structural biology.

<span class="mw-page-title-main">Cryogenic electron tomography</span>

Cryogenic electron tomography (cryoET) is an imaging technique used to reconstruct high-resolution (~1–4 nm) three-dimensional volumes of samples, often biological macromolecules and cells. cryoET is a specialized application of transmission electron cryomicroscopy (CryoTEM) in which samples are imaged as they are tilted, resulting in a series of 2D images that can be combined to produce a 3D reconstruction, similar to a CT scan of the human body. In contrast to other electron tomography techniques, samples are imaged under cryogenic conditions. For cellular material, the structure is immobilized in non-crystalline, vitreous ice, allowing them to be imaged without dehydration or chemical fixation, which would otherwise disrupt or distort biological structures.

Michael G. Rossmann was a German-American physicist, microbiologist, and Hanley Distinguished Professor of Biological Sciences at Purdue University who led a team of researchers to be the first to map the structure of a human common cold virus to an atomic level. He also discovered the Rossmann fold protein motif. His most well recognised contribution to structural biology is the development of a phasing technique named molecular replacement, which has led to about three quarters of depositions in the Protein Data Bank.

<i>Cowpea chlorotic mottle virus</i> Species of virus

Cowpea chlorotic mottle virus, known by the abbreviation CCMV, is a virus that specifically infects the cowpea plant, or black-eyed pea. The leaves of infected plants develop yellow spots, hence the name "chlorotic". Similar to its "brother" virus, Cowpea mosaic virus (CPMV), CCMV is produced in high yield in plants. In the natural host, viral particles can be produced at 1–2 mg per gram of infected leaf tissue. Belonging to the bromovirus genus, cowpea chlorotic mottle virus (CCMV) is a small spherical plant virus. Other members of this genus include the brome mosaic virus (BMV) and the broad bean mottle virus (BBMV).

HHV Capsid Portal Protein, or HSV-1 UL-6 protein, is the protein which forms a cylindrical portal in the capsid of Herpes simplex virus (HSV-1). The protein is commonly referred to as the HSV-1 UL-6 protein because it is the transcription product of Herpes gene UL-6.

<span class="mw-page-title-main">Double-stranded RNA viruses</span> Type of virus according to Baltimore classification

Double-stranded RNA viruses are a polyphyletic group of viruses that have double-stranded genomes made of ribonucleic acid. The double-stranded genome is used as a template by the viral RNA-dependent RNA polymerase (RdRp) to transcribe a positive-strand RNA functioning as messenger RNA (mRNA) for the host cell's ribosomes, which translate it into viral proteins. The positive-strand RNA can also be replicated by the RdRp to create a new double-stranded viral genome.

<span class="mw-page-title-main">P24 capsid protein</span>

The P24 capsid protein is the most abundant HIV protein with each virus containing approximately 1,500 to 3,000 p24 molecules. It is the major structural protein within the capsid, and it is involved in maintaining the structural integrity of the virus and facilitating various stages of the viral life cycle, including viral entry into host cells and the release of new virus particles. Detection of p24 protein's antigen can be used to identify the presence of HIV in a person's blood, however, more modern tests have taken their place. After approximately 50 days of infection, the p24 antigen is often cleared from the bloodstream entirely.

Resolution in the context of structural biology is the ability to distinguish the presence or absence of atoms or groups of atoms in a biomolecular structure. Usually, the structure originates from methods such as X-ray crystallography, electron crystallography, or cryo-electron microscopy. The resolution is measured of the "map" of the structure produced from experiment, where an atomic model would then be fit into. Due to their different natures and interactions with matter, in X-ray methods the map produced is of the electron density of the system, whereas in electron methods the map is of the electrostatic potential of the system. In both cases, atomic positions are assumed similarly.

<i>Sulfolobus turreted icosahedral virus 1</i> Species of virus

Sulfolobus turreted icosahedral virus 1 is a species of virus that infects the archaeon Sulfolobus solfataricus.

<i>Clavaviridae</i> Family of viruses

Clavaviridae is a family of double-stranded viruses that infect archaea. This family was first described by the team led by D. Prangishvili in 2010. There is one genus in this family (Clavavirus). Within this genus, a single species has been described to date: Aeropyrum pernix bacilliform virus 1 (APBV1).

<span class="mw-page-title-main">Macromolecular assembly</span>

The term macromolecular assembly (MA) refers to massive chemical structures such as viruses and non-biologic nanoparticles, cellular organelles and membranes and ribosomes, etc. that are complex mixtures of polypeptide, polynucleotide, polysaccharide or other polymeric macromolecules. They are generally of more than one of these types, and the mixtures are defined spatially, and with regard to their underlying chemical composition and structure. Macromolecules are found in living and nonliving things, and are composed of many hundreds or thousands of atoms held together by covalent bonds; they are often characterized by repeating units. Assemblies of these can likewise be biologic or non-biologic, though the MA term is more commonly applied in biology, and the term supramolecular assembly is more often applied in non-biologic contexts. MAs of macromolecules are held in their defined forms by non-covalent intermolecular interactions, and can be in either non-repeating structures, or in repeating linear, circular, spiral, or other patterns. The process by which MAs are formed has been termed molecular self-assembly, a term especially applied in non-biologic contexts. A wide variety of physical/biophysical, chemical/biochemical, and computational methods exist for the study of MA; given the scale of MAs, efforts to elaborate their composition and structure and discern mechanisms underlying their functions are at the forefront of modern structure science.

Tristromaviridae is a family of viruses. Archaea of the genera Thermoproteus and Pyrobaculum serve as natural hosts. Tristromaviridae is the sole family in the order Primavirales. There are two genera and three species in the family.

<span class="mw-page-title-main">Cryogenic electron microscopy</span> Form of transmission electron microscopy (TEM)

Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid ethane or a mixture of liquid ethane and propane. While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution. This has attracted wide attention to the approach as an alternative to X-ray crystallography or NMR spectroscopy for macromolecular structure determination without the need for crystallization.

Microcrystal electron diffraction, or MicroED, is a CryoEM method that was developed by the Gonen laboratory in late 2013 at the Janelia Research Campus of the Howard Hughes Medical Institute. MicroED is a form of electron crystallography where thin 3D crystals are used for structure determination by electron diffraction. Prior to this demonstration, macromolecular (protein) electron crystallography was mainly used on 2D crystals, for example. The method is one of several modern versions of approaches to determine atomic structures using electron diffraction first demonstrated for the positions of hydrogen atoms in NH4Cl crystals by W. E. Laschkarew and I. D. Usykin in 1933, which has since been used for surfaces, via precession electron diffraction, with much of the early work described in the work of Boris Vainshtein and Douglas L. Dorset.

Mavis Agbandje-McKenna was a Nigerian-born British medical biophysicist, structural virologist, and a professor of structural biology, as well as the director of the Center for Structural Biology at the University of Florida in Gainesville, Florida. Agbandje-McKenna studied parvovirus structures using X-ray crystallography and cryogenic electron microscopy and did much of the initial work to elucidate the basic structure and function of adeno-associated viruses (AAVs). Her viral characterization and elucidation of antibody binding sites on AAV capsids has led to the development of viral capsid development and gene therapy approaches that evade immune detection and can be used to treat human diseases such as muscular dystrophies. Agbandje-McKenna was recognized with the 2020 American Society of Gene and Cell Therapy Outstanding Achievement Award for her contributions to the field. She died in 2021 from amyotrophic lateral sclerosis.

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